Leber congenital amaurosis (LCA) is an inherited eye disorder that primarily affects the retina, a specialized neuronal tissue at the back of the eye that detects light and color. People with this disease have severe visual impairment beginning in infancy. It occurs in 1 per 50,000 newborns and is one of the most common causes of blindness in children. So far, LCA-disease causing mutations have been identified in twenty-one genes. Mutations in the Centrosomal Protein 290 (CEP290) (NP_079390) gene account for 20-25 percent of LCA, afflicting an estimated 20,000 people worldwide. There is no treatment for this disease to date.
In recent years, gene therapy has emerged as a promising treatment modality for inherited eye disorders. Functional improvement has been achieved by gene therapy in patients with mutations in another gene, RPE65, which accounts for about 5% of LCA. Gene therapy for CEP290-related LCA (i.e., LCA caused by mutations in the CEP290 gene) has not been successful, even in animal models of the disease. A major reason for this lack of success is the difficulty of delivering the correct copy of CEP290 gene into the diseased retina due to the large size of the complete coding region. To treat LCA patients with CEP290 mutations, a correct copy of the CEP290 gene needs to be transferred into the patients' photoreceptor cells in their retinas. But the 7.4 kb size of the wild-type CEP290 cDNA significantly hampers its delivery into photoreceptors in the eye. Consequently, there is a need for an efficient treatment of CEP290-related LCA. The present invention addressees this need and achieves other advantages, which are discussed more fully below.